High-content screening in zebrafish identifies perfluorooctanesulfonamide as a potent developmental toxicant
High-content screening in zebrafish identifies perfluorooctanesulfonamide as a potent developmental toxicant
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DOI：
10.1016/j.envpol.2019.113550
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发表时间：
2020-01-01
影响因子：
8.9
通讯作者：
Volz, David C.
中科院分区：
文献类型：
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作者：
Dasgupta, Subham;Reddam, Aalekhya;Volz, David C.
全氟烷基和多氟烷基物质（PFAS）已在工业过程和消费品中使用了几十年，导致在环境中频繁检测到。使用斑马鱼胚胎，我们筛选了38种PFAS的发育毒性，并发现全氟辛烷磺酰胺（PFOSA）是最有效的发育毒物，导致受精后6至24小时（hpf）和6至72 hpf暴露后死亡率升高和发育异常。PFOSA导致死亡率和畸形率呈浓度依赖性增加，存活胚胎在24 hpf时发育延迟>12小时。在0.75 hpf开始的暴露也导致了外延的浓度依赖性延迟，尽管这些效应不是由特定的敏感发育窗口驱动的。我们依靠mRNA测序来确定PFOSA诱导的发育延迟与胚胎转录组影响的潜在关联。相对于阶段匹配的载体对照，这些数据显示，在胚胎暴露于PFOSA 0.75至14 hpf和0.75至24 hpf时，与肝毒性和脂质转运相关的途径被破坏。因此，我们测量了128-hpf胚胎暴露于溶剂（0.1%DMSO）或PFOSA（0.75 - 24 hpf）和清洁水（24 - 128 hpf）时的肝脏面积和中性脂质，结果表明，PFOSA暴露于0.75 - 24 hpf时导致肝脏面积减少，128 hpf时卵黄囊中性脂质增加。总的来说，我们的研究结果表明，早期暴露于PFOSA对胚胎发育产生不利影响，这种影响可能导致脂质转运和肝脏发育的改变。(C)2019爱思唯尔有限公司版权所有。
Per- and polyfluoroalkyl substances (PFASs) have been used for decades within industrial processes and consumer products, resulting in frequent detection within the environment. Using zebrafish embryos, we screened 38 PFASs for developmental toxicity and revealed that perfluorooctanesulfonamide (PFOSA) was the most potent developmental toxicant, resulting in elevated mortality and developmental abnormalities following exposure from 6 to 24 h post fertilization (hpf) and 6 to 72 hpf. PFOSA resulted in a concentration-dependent increase in mortality and abnormalities, with surviving embryos exhibiting a >12-h delay in development at 24 hpf. Exposures initiated at 0.75 hpf also resulted in a concentrationdependent delay in epiboly, although these effects were not driven by a specific sensitive window of development. We relied on mRNA-sequencing to identify the potential association of PFOSA-induced developmental delays with impacts on the embryonic transcriptome. Relative to stage-matched vehicle controls, these data revealed that pathways related to hepatotoxicity and lipid transport were disrupted in embryos exposed to PFOSA from 0.75 to 14 hpf and 0.75 to 24 hpf. Therefore, we measured liver area as well as neutral lipids in 128-hpf embryos exposed to vehicle (0.1% DMSO) or PFOSA from 0.75 to 24 hpf and clean water from 24 to 128 hpf, and showed that PFOSA exposure from 0.75 to 24 hpf resulted in a decrease in liver area and increase in yolk sac neutral lipids at 128 hpf. Overall, our findings show that early exposure to PFOSA adversely impacts embryogenesis, an effect that may lead to altered lipid transport and liver development. (C) 2019 Elsevier Ltd. All rights reserved.